title: Generation of demyelination models by targeted ablation of oligodendrocytes in the zebrafish CNS.
abstract: Demyelination is the pathological process by which myelin sheaths are lost from around axons, and is usually caused by a direct insult targeted at the oligodendrocytes in the vertebrate central nervous system (CNS). A demyelinated CNS is usually remyelinated by a population of oligodendrocyte progenitor cells, which are widely distributed throughout the adult CNS. However, myelin disruption and remyelination failure affect the normal function of the nervous system, causing human diseases such as multiple sclerosis. In spite of numerous studies aimed at understanding the remyelination process, many questions still remain unanswered. Therefore, to study remyelination mechanisms in vivo, a demyelination animal model was generated using a transgenic zebrafish system in which oligodendrocytes are conditionally ablated in the larval and adult CNS. In this transgenic system, bacterial nitroreductase enzyme (NTR), which converts the prodrug metronidazole (Mtz) into a cytotoxic DNA cross-linking agent, is expressed in oligodendrocyte lineage cells under the control of the mbp and sox10 promoter. Exposure of transgenic zebrafish to Mtz-containing media resulted in rapid ablation of oligodendrocytes and CNS demyelination within 48 h, but removal of Mtz medium led to efficient remyelination of the demyelinated CNS within 7 days. In addition, the demyelination and remyelination processes could be easily observed in living transgenic zebrafish by detecting the fluorescent protein, mCherry, indicating that this transgenic system can be used as a valuable animal model to study the remyelination process in vivo, and to conduct high-throughput primary screens for new drugs that facilitate remyelination.
authors.affiliation: Graduate School of Medicine, Korea University, Ansan, 425-707, Korea.
authors.forename: Ah-Young
authors.initials: AY
authors.lastname: Chung
authors.forename: Pan-Soo
authors.initials: PS
authors.lastname: Kim
authors.forename: Suhyun
authors.initials: S
authors.lastname: Kim
authors.forename: Eunmi
authors.initials: E
authors.lastname: Kim
authors.forename: Dohyun
authors.initials: D
authors.lastname: Kim
authors.forename: Inyoung
authors.initials: I
authors.lastname: Jeong
authors.forename: Hwan-Ki
authors.initials: HK
authors.lastname: Kim
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Ryu
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: June
authors.initials: J
authors.lastname: Choi
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Seo
authors.forename: Hae-Chul
authors.initials: HC
authors.lastname: Park
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019070:Cell Lineage; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology*; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D015027:Zebrafish / Q000378:metabolism*; D000097573:Red Fluorescent Protein
chemical_list: D008164:Luminescent Proteins; D015534:Trans-Activators; D000097573:Red Fluorescent Protein; C070633:Gal-VP16